The mechanisms by which cadmium induces tumor formation are under study. On the cellular level, pretreatments such as high dose zinc or low dose cadmium that are known to prevent testicular tumorigenesis in vivo were found to drastically reduce the adverse effects of cadmium on isolated testicular cells in vitro. Zinc pretreatment markedly reduced the interactions of cadmium with testicular interstitial cell chromatin and DNA. Neither low dose cadmium nor high dose zinc had any effect on levels of the cadmium-binding protein seen in place of metallothionein in the testes. Likewise, metallothionein was found to be deficient in the rat prostate, a recently defined target site of cadmium carcinogenesis. Metallothionein mRNA levels in testes were unresponsive to stimuli, including cadmium or zinc exposure, that cause marked increases in translation of the metallothionein gene in tissues where its synthesis is established, such as liver. In long-term carcinogenesis studies, repeated exposures to cadmium proved to stimulate malignancy as both interstitial cell and injection site tumors proved highly metastatic with repeated cadmium treatments. A marked increase in tumors of the lymph system, including rat leukemia and mouse lymphomas, was also seen with cadmium treatment, establishing this tissue as another target site of cadmium carcinogenesis. A potential animal model of cadmium carcinogenesis in the kidney, a suspected human target site of cadmium, was detected in Syrian hamsters which proved uniquely susceptible to the acute renal effects of cadmium.